Water-soluble package

ABSTRACT

A water-soluble package is provided in the form of a hard shell capsule filled with powder, granules, or the like. The capsule shell is apertured, and the apertures or holes are covered over by a water-soluble barrier film which seals the holes and blocks any escape of the contents from the shell. The film is more water-soluble than the cap and body parts of the shell so that when the package is contacted with water, as in the digestive tract, the film rather than the shell dissolves first exposing the contents for dissolution and/or release by way of the apertures while the shell is still intact.

United States Patent [191 Controulis et a1.

WATER-SOLUBLE PACKAGE Inventors: John Controulis, Grosse Pointe Farms; Kenneth N. Larsen, Southfield; Larry M. Wheeler, Grosse Pointe Farms, all of Mich.

Parke, Davis & Company, Detroit, Mich.

Filed: Feb. 3, 1972 Appl. No.: 223,123

Assignee:

' us. c1 206/.5, 206/438, 424/15,

Int. Cl A61I 9/04 Field of Search 99/78, 171 B, 66, 71, 77.1, 99/166; 424/15, 16, 31, 32, 21; 206/5, 46 F, 63.2 R, 84

References Cited UNITED STATES PATENTS 12/1919 Goldsworthy 99/77.l 10/1921 Scott 99/71 2/1925 Scott 424/21 3/1926 Fessenden.... 99/77.1 10/1933 Leever 99/78 [451 July 16, 1974 2,292,101 8/1942 Brown 99/77.l

2,537,453 l/1951 Frangialli 99/78 3,620,759 11/1971 Maddox 99/78 OTHER PUBLICATIONS Condensed Chem. Dict., 761 Ed., 1966, pages 769-770.

Primary Examiner-Morris O. WoIk Assistant Examiner-Sidney Marantz 5 7] ABSTRACT A water-soluble package is provided in the formof a hard shell capsule filled with powder, granules, or the like. The capsule shell is apertured, and the apertures or holes are covered over by a water-soluble barrier film which seals the holes and blocks any escape of the contents from the shell. The film is more watersoluble than the cap and body parts of the shell so that when thepackage is contacted with water, as in the digestive tract, the film rather than the shell dissolves first exposing the contents for dissolution and/or release by way of the apertures while the shell is still intact.

6 Claims, 3 Drawing Figures I SUMMARY AND DETAILED DESCRIPTION This invention relates to a novel water-soluble or water-reactive package in the form of an apertured cap and body capsule containing a particulate solid fill.

In the prior art, capsules have been a preferred means for packaging dry powder, granules or other particulate matter. However, where it was desired to achieve quick release of the contents in water, the objective was in some instances not obtained because the capsule shell remained intact and failed to dissolve as quickly as desired. On the other hand, where access holes or apertures were provided in the capsule wall (in preparation for eventual contact with water to accelerate wetting and dissolving of the contents) the apertures allowed the dry contents to leak out. While the slightest leakage is intolerable for many applications, fast-release loss-proof capsules have hitherto not been available.

It is therefore an object of the present invention to provide a novel water-soluble package in the form of an apertured capsule for particulate matter, powders, granules or the like. v

It is also an object of the invention to provide a packaged particulate substance in a form which, intact prior to use, is completely dissolved or slurried within relatively short periods when contacted with or exposed to water, gastrointestinal fluid, etc.

These and other objects, purposes and advantages of the invention will be seen from the following description in relation to the accompanying drawing in which:

FIG. 1 is a side view of a packaged article according to a preferred embodiment of the invention;

FIG. 2 is a fragmented expanded view in vertical section taken on line 2--2 of F IG. 1 showing the construction of the sealed wall of the article; and

FIG. 3 is a plan view of the article when incorporated with a body of water according to the invention.

Referring to FIG. 1, the article in the form illustrated has a cap part 11 and a matching telescopicallyengaged body part 12 which together provide a closed envelope shell. As with conventional capsules, the cap 11 and the body 12 each have open ends (not shown) and closed ends 11b and 12b as well as cylindrical walls 110 and 120. The walls overlap in a double-walled portion 13. The capsule shell contains a particulate fill l4, and the walls include aperture means 15 extending through the thickness (FIG. 2, single or double wall) toprovide open communication'with the ,shell interior containing the fill 14. A continuous film or barrier 17 overlies each aperture means 15 and seals the same. The film is in a single strip form covering a row of apertures, as illustrated in FIG. 1. The film 17 is generallyof uniform thickness, being slightly thicker within the, margin of the apertures where it occupies the spacewithin each aperture in the form of plugs 16 (FIG.'2). The film can, according to the invention, have various shapes and is not limited to the strip shape illustrated.

For example, it may conveniently cover the entire outer surface of the capsule or it may cover discontinuqi sal a s qh EQYQFELEE. siss seaata e 9255992 9 apertures. In any event, the shape should be such that it alone, or in combination with other barrier films (having the same or different shapes), completely covers and seals all of the apertures. It is an advantageous feature that in the embodiment where the barrier film covers both the cap and body surface, for example, in a single strip (as in FIGS. 1 and 2) or the entire capsule surface, the film serves to lock the capsule parts to- 'gether.

The packaged articles of the invention are conveniently prepared in several steps. First, empty capsules (preferably pharmaceutical-grade gelatin or an equivalent) are filled with the selected particulate substance (e.g., medicament, chemical, or other substance) and are joined, using conventional means. The apertures 15 are then made in the filled joined capsules in a perforating step, using any suitable hole-forming means such as heated needles, knives, drills or the like. The apertured filled capsules are next treated with a liquid solution of the film-forming substance as by spraying, dipping, brushing, printing or the like to produce the desired film bridging and sealing the holes in the capsule wall. Any of various water-soluble film-forming substances will be suitable for the purpose such as polyvinylpyrrolidone, gelatin, hydroxypropylmethyl. cellulose, hydroxymethylethyl cellulose, ethyl cellulose, hydroxypropyl cellulose or the like or mixtures thereof. Polyvinylpyrrolidone is a preferred film-forming substance. Conveniently, it is used for film-forming purposes as a dilute (e.g., 5-10 percent) aqueous or alcoholic solution and the capsules to be film-coated are dipped in a bath of the solution to completely coat the outer surface of each capsule with the film solution. Area coating, such as the preferred strip configuration 17 illustrated in FIG. 1, can be printed as a moist film over the apertures using conventional machinery. The coating film following application is dried until tack-free and sufficiently firm and-dimensionally stable to seal the apertures and prevent escape of the granular fill.

The size, shape, number and distribution of the apertures 15 in the capsule shell can be varied widely, as desired. Aperture sizes made with hypodermic needles, for example, ranging from No. 27 (OD, 0.41 mm.) to No. 21 (0.81 mm.) have been particularly satisfactory. The holes can be round, crescent-shaped, square, etc although round holes are preferred. Numerous holes can be used, and the distribution can be spaced over the end and/or wall surfaces of the capsule. However, in general it is found that from one to six aperturesin the capsule issufficient for purposes of the invention. The in-line configuration illustrated is one preferred embodiment, usually with two to six apertures. Another preferred embodiment is a single-hole configuration centered at one or both ends of the capsule shell. In test procedures measuring solubility. and release in warm water (37 C.) the following results were obtained using capsules filled with a dry powder, joined, perforated, and either uncoated or coated with polyvinylpyrrolidone film and air-dried. The results are given in tenns of the times required for initial rupture or disso lution of the film coating and for final disintegration of thesbslland utente Final Capsule Description Test Aperture Aperture Time for Disintegra: No. Configuration Size Coating Initial Rupture tion time I 6 holes 25 gauge no sec. l min.

.. w-.. A i H malJz dyii septhatqsili msl.se tin Nol 1, blue opaque cap, clear body, pharmaceutical-grade gelatin.

Caggqle" Descg'gtion Fina] Test Aperture Aperture Time for Disinteg'm N Configuration IZC Coating Initial Rupture tion time 2 6 holes do. total di 50 sec. 2 i (3 body, 3 cap) 1 coating in 35 alcohol PVP soln. 3 6 holes do brush 40 sec. l 3 min. (3 body, 3 cap) coating sec.

water- PVP 10%) soln. 4 1 hole (cap) 27 gauge brush 1 min. 4 min. (0.41 mm.) coating sec. 15 sec.

. alcohol- PVP (l0%) soln. 5 4 holes 26 gauge do. 50 sec. 3 min. (2 body, 2 cap) (0.46 mm.) 15sec. 6 2 holes do. do. 1 min. 3 min. (1 body, I cap) 7 10 sec. 40sec. 7 1 hole 25 gauge do. 53 sec. 4 min. (body end) 20 sec. 8 2 holes 21 auge do. 40 sec. 3 min. (l body, 1 cap) (0.8 mm.) 35 sec. 9 6 holes do. do. 35 sec. 2 min.

(body only) 45 sec.

These results show that conventional capsules, modified by perforation with six holes but without a film coating (Test No. 1) released their contents in short periods when incorporated with water. Initial rupture typically took place in 45 seconds. Final disintegration, i.e., complete dissolution of capsules and contents in water, took place in less than 2 minutes. However, the dry capsules were unsatisfactory because of an unsightly dusty appearance with powder leakage, etc. In contrast, sealed aperture capsules according to the invention (Test Nos. 2-9) had a clean appearance (without leakage) resembling the finish of conventional filled capsules. They'p'erformed well in terms of water rupture and final disintegration, by comparison with conventional non-apertured capsules which when exposed to water under the same conditions typically failed to rupture even after extended periods of 20 minutes or more.

The invention contemplates as contents for the package or capsule any particulate substance which, al-

, though inert to the shell or envelope, is reactive-or soluble in water or any of various aqueous media such as gastro-intestinal fluid. The invention is particularly well-suited in this respect to particulate fill material, which effervesces in the presence of water either as an active ingredient, for example, of a, pharmaceutical dosage form or as an aid per se to promote a mixing or dissolving effect for other components in the fill. In regard to the characteristics of the sealed aperture capsules of the invention when exposed to water, the typical capsule filled, for example, with low density powder usually floats (capsule A, FIG. 3) on the surface 20'of the water. Unless stirred or otherwise moved, the capsule remains afloat for a brief period until the film 17 is wetted and dissolved in the area of the apertures 15. Advantageously, when this occurs, the capsule sinks of its own accord into the body 21 of the liquid (capsule B, FIG. 3) while the dissolving and release actions continue and, because of the increased wetting contact, even at a greater rate. The dissolving action is such that ordinarily a capsule of the kind illustrated (apertured in both the cap and the body) is completely consumed withinzf mia lqsn- While the invention insealed aperture capsules has been described in considerable detail, it'will be realized by those skilled in the art that wide'variation in such detail can be made withoutdeparting from the spirit of the invention as claimed below, and it is intended the claims should be interpreted to cover the invention as described and any such variation.

' We claim: I v

1. In an ingestible water-reactive unit package including a cylindrical hard shell capsule having matching water-soluble cap and body parts telescopically joined to define a closed envelope shell, the cap and body each having an open end, a closed end, and side walls overlapping in a double-walled portion, a particulate solid fill in the shell, and aperture means in the shell providing open communication between the interior and the exterior of the shell, the improvement characterized by a water-soluble barrier in the form of a dimensionally stable film bridging the aperture means comprising a plurality of apertures located in line, the film occupying space within each aperture in the form of plugs in sealing engagement therewith sufficient to block escape of solid fill from the shell, the barrier being substantially more water-soluble than the cap and body parts such that continued contact of the package with water in an aqueous environment causes the barrier to dissolve prior to dissolution of the shell thereby affording direct access of water to the fill while the shell is intact.

2. A package according to claim lwherein the rier film is a polyvinylpyrrolidone film.

3. A package according to claim 1 wherein the apertures are covered by the barrier film in the form of a strip.

4. A package according to claim 1 wherein the aperture means comprises at least one aperture located at the end of the capsule.

5. A package according to claim l.-wherein the capsule is a pharmaceutical-grade gelatin capsule.

6. A package according to claim 1 wherein the fill includes a substance which effervesces in the presence of water. I

bar- 

2. A package according to claim 1 wherein the barrier film is a polyvinylpyrrolidone film.
 3. A package according to claim 1 wherein the apertures are covered by the barrier film in the form of a strip.
 4. A package according to claim 1 wherein the aperture means comprises at least one aperture located at the end of the capsule.
 5. A package according to claim 1 wherein the capsule is a pharmaceutical-grade gelatin capsule.
 6. A package according to claim 1 wherein the fill includes a substance which effervesces in the presence of water. 